CEINGE Biotecnologie Avanzate, Napoli, Italy.
Am J Hematol. 2011 Sep;86(9):727-32. doi: 10.1002/ajh.22096.
Congenital Dyserythropoietic Anemia type II is an autosomal recessive disorder characterized by unique abnormalities in the differentiation of cells of the erythroid lineage. The vast majority of CDA II cases result from mutations in the SEC23B gene. To date, 53 different causative mutations have been reported in 86 unrelated cases (from the CDA II European Registry), 47 of them Italian. We have now identified SEC23B mutations in 23 additional patients, 17 Italians and 6 non-Italian Europeans. The relative allelic frequency of the mutations was then reassessed in a total of 64 Italian and 45 non-Italian unrelated patients. Two mutations, E109K and R14W, account for over one-half of the cases of CDA II in Italy. Whereas the relative frequency of E109K is similar in Italy and in the rest of Europe (and is also prevalent in Moroccan Jews), the relative frequency of R14W is significantly higher in Italy (26.3% vs. 10.7%). By haplotype analysis we demonstrated that both are founder mutations in the Italian population. By using the DMLE+ program our estimate for the age of the E109K mutation in Italian population is ≈2,200 years; whereas for the R14W mutation it is ≈3,000 years. We hypothesize that E109K may have originated in the Middle East and may have spread in the heyday of the Roman Empire. Instead, R14W may have originated in Southern Italy. The relatively high frequency of the R14W mutation may account for the known increased prevalence of CDA II in Italy.
先天性红细胞生成异常性贫血 II 型是一种常染色体隐性遗传病，其特征是红系细胞分化的独特异常。绝大多数 CDA II 病例是由 SEC23B 基因突变引起的。迄今为止，在 86 个无关病例（来自 CDA II 欧洲登记处）中已报道了 53 种不同的致病突变，其中 47 种来自意大利。我们现在已经在 23 名额外的患者中发现了 SEC23B 突变，其中 17 名是意大利人，6 名是非意大利欧洲人。然后，我们在总共 64 名意大利和 45 名非意大利无关患者中重新评估了突变的相对等位基因频率。E109K 和 R14W 两种突变占意大利 CDA II 病例的一半以上。虽然 E109K 在意大利和欧洲其他地区的相对频率相似（并且在摩洛哥犹太人中也很普遍），但 R14W 的相对频率在意大利明显更高（26.3%比 10.7%）。通过单倍型分析，我们证明这两种突变都是意大利人群中的起源突变。通过使用 DMLE+程序，我们估计 E109K 突变在意大利人群中的年龄约为 2200 年；而对于 R14W 突变，它的年龄约为 3000 年。我们假设 E109K 可能起源于中东，并可能在罗马帝国的鼎盛时期传播。相反，R14W 可能起源于意大利南部。R14W 突变的相对高频率可能解释了已知的 CDA II 在意大利的发病率增加。
